As a next-generation DNA sequencer, a method for electrically directly measuring a DNA base sequence without elongation reaction and fluorescent label has attracted attention. In order to realize the above measuring method, the research and development of a nanopore DNA sequencing method for directly measuring a DNA fragment without the use of reagent to determine the base sequence has been actively advanced. The above method is based on a principle that when a DNA chain passes through a nanopore, a difference of the individual base types contained in the DNA chain is directly measured by a blockage current amount to sequentially identify the base types. Since amplification of a template DNA by enzyme is not carried out and no labeling substances such as fluorescent substances are used, the above method is expected to lead to a high throughput, a low running cost, and a long base length decoding.
One of the challenges of the nanopore method is transport control of the DNA that passes through the nanopore. In order to measure a difference between the individual base types contained in the DNA chain according to the blockade current amount, it is conceivable that a nanopore passage speed of the DNA is set to 100 μs or more per base according to a current noise at the time of measurement and a time constant of the fluctuation of DNA molecules. When sequencing DNA with the use of the nanopore, a potential gradient is formed with the use of electrodes located above and below the nanopore, and the DNA with a negative charge is allowed to pass through the nanopore. However, the nanopore passage speed of the DNA is usually as fast as 1 μs or less per base, which makes it difficult to sufficiently measure the blockade current derived from each base.
As one of the transport control methods, the DNA terminal to be read is immobilized at a leading end of an immobilized probe and minute displacement of the immobilized probe is controlled by an external drive mechanism (motor and piezo element), to thereby control the movement of the DNA passing through the nanopore.